Project Summary The discovery of new antimicrobials has failed to keep pace with the emergence of antimicrobial-resistant infections, threatening public health. The overarching goal of the Wisconsin Antimicrobial Drug Discovery and Development Center is to develop therapeutic countermeasures to tackle the antimicrobial resistance crisis. Based upon our preliminary investigations using interdisciplinary, cutting-edge approaches, we hypothesize that natural products from animal-microbe symbioses represent a new paradigm in antimicrobial drug discovery. The Center proposes innovative conceptual and technical advances to overcome the critical bottlenecks of traditional antimicrobial discovery to deliver therapeutic countermeasures for the drug-resistance epidemic. Relevance There is an ever-present and growing need to find novel, effective therapies for emerging resistant pathogens that are becoming an increasing threat to the public health. The goals of the Center are to discover new antimicrobial drugs. Our collaborative effort focuses on high-value natural products produced by under- explored sources of biological and chemical diversity.